RRC ID 76112
Author Aman Y, Erinjeri AP, Tataridas-Pallas N, Williams R, Wellman R, Chapman H, Labbadia J.
Title Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors.
Journal Cell Rep
Abstract The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases.
Volume 41(8)
Pages 111690
Published 2022-11-22
DOI 10.1016/j.celrep.2022.111690
PII S2211-1247(22)01564-9
PMID 36417880
MeSH Animals Apoptosis Caenorhabditis elegans / metabolism Protein Folding Proteome* / metabolism Proteostasis* / physiology
C.elegans tm1108